Renal Impairment Does Not Affect Pharmacokinetics, Safety or Tolerability of Zenagamtide.
Renal impairment does not appear to significantly affect the pharmacokinetics or safety of zenagamtide, indicating no need for dose adjustment in these patients.
Where it sits
this study against the rest of the zenagamtide corpusSummary and findings
This study measured the pharmacokinetics, safety, and tolerability of zenagamtide in adults with varying degrees of renal impairment compared to those with normal renal function. Participants received a single subcutaneous dose of 0.3 mg zenagamtide. The findings suggest renal impairment did not significantly affect the pharmacokinetics or safety profile of zenagamtide.
Abstract
<h4>Aims</h4>Zenagamtide is a novel, unimolecular glucagon-like peptide-1 and amylin receptor agonist in development for weight management and Type 2 diabetes. This study investigated the pharmacokinetic (PK) properties, safety and tolerability of zenagamtide in participants with various degrees of renal impairment versus participants with normal renal function.<h4>Materials and methods</h4>Adults with body mass index 20.0-39.9 kg/m<sup>2</sup> were categorised based on baseline renal status using the CKD-EPI Collaboration creatinine equation (2021); normal function, mild impairment, moderate impairment, severe impairment and end-stage renal disease (ESRD). Participants received a single subcutaneous dose of zenagamtide 0.3 mg, followed by a 4-week follow-up period. The primary endpoint was area under the zenagamtide plasma concentration-time curve from time zero to infinity (AUC<sub>0-∞</sub>). Additional endpoints included maximum observed plasma zenagamtide concentration (C<sub>max</sub>) and number of treatment-emergent adverse events (TEAEs).<h4>Results</h4>In total, 42 participants were included (n = 14, normal renal function group; n = 7 per renal impairment group). The range (geometric mean) of zenagamtide AUC<sub>0-∞</sub> and C<sub>max</sub> across renal impairment groups were 520-715 h × nmol/L and 2.8-3.5 nmol versus 543 h × nmol/L and 3.2 nmol/L for the normal renal function group, respectively. Overall, TEAEs were reported in 30 (71.4%) participants. TEAEs were non-serious, none were severe and the majority were mild and most frequently gastrointestinal in nature.<h4>Conclusions</h4>Renal impairment did not appear to have a clinically relevant impact on the PK or safety profile of zenagamtide, suggesting that dose adjustment of zenagamtide is not warranted in this population.<h4>Trial registration</h4>ClinicalTrials.gov: NCT06559527.
Background
This paper addresses the pharmacokinetic properties and safety of zenagamtide, a glucagon-like peptide-1 and amylin receptor agonist, particularly in the context of renal impairment. Prior research has indicated that renal function can influence the pharmacokinetics of various drugs, making this study relevant for understanding zenagamtide's use in patients with kidney issues. The findings could inform dosing recommendations for individuals with renal impairment.
Methods
The study employed a comparative design involving adults with a body mass index of 20.0-39.9 kg/m², categorized by renal function using the CKD-EPI Collaboration creatinine equation. A total of 42 participants were included, with 14 in the normal renal function group and 7 in each renal impairment group. Participants received a single subcutaneous dose of 0.3 mg zenagamtide, followed by a 4-week follow-up period. The primary endpoint was the area under the plasma concentration-time curve (AUC0-∞), with additional endpoints including maximum observed plasma concentration (Cmax) and treatment-emergent adverse events (TEAEs).
Results
The primary endpoint, AUC0-∞, ranged from 520-715 h × nmol/L in the renal impairment groups, compared to 543 h × nmol/L in the normal renal function group. Cmax values ranged from 2.8-3.5 nmol/L for the renal impairment groups versus 3.2 nmol/L for the normal group. A total of 30 participants (71.4%) reported TEAEs, which were predominantly mild and gastrointestinal in nature.
Interpretation
The results indicate that renal impairment does not significantly alter the pharmacokinetics or safety of zenagamtide, suggesting that no dose adjustment is necessary in this population. However, the small sample size and short follow-up period limit the robustness of these conclusions. Compared to existing literature, these findings contribute to the understanding of zenagamtide's safety profile in patients with renal issues, but further studies are needed to confirm these results.
Key findings
- AUC0-∞ ranged from 520-715 h × nmol/L across renal impairment groups versus 543 h × nmol/L for normal renal function group.
- Cmax ranged from 2.8-3.5 nmol/L across renal impairment groups versus 3.2 nmol/L for normal renal function group.
- 30 (71.4%) participants reported treatment-emergent adverse events (TEAEs).
- TEAEs were non-serious, with none classified as severe, and most were mild and gastrointestinal in nature.
Limitations
- small sample size with n=42
- only 7 participants per renal impairment group
- 4-week follow-up may not capture long-term effects
- non-serious TEAEs reported, limiting safety assessment